Doctor of Medicine Research Proves Molecular Mechanism of High Grade Tumor Budding in Cervical Carcinoma

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• Selasa, 26 Maret 2024
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Located in the Dr. A.A Made Djelantik Room of the Faculty of Medicine, Udayana University, Sudirman Campus, Denpasar Bali, a Doctoral Promotion examination was held with Promovenda candidate Dr. Ni Wayan Armerinayanti, M.Biomed., Sp.PA., with the dissertation title "Overexpression of Micro-RNA 21 (miR-21), High Expression of Protein 53 (p53) and Matrix Metaloproteinase 9 (MMP-9) is a Risk Factor for High Grade Tumor Budding in Cervical Carcinoma." (25/3/2024)

High grade tumor budding is a controversial parameter in determining the aggressiveness of cervical carcinoma. Only a few studies have explored the molecular mechanism of tumor budding. MicroRNA 21 (miR-21) is one of the epigenetic factors that can cause downregulation of many tumor suppressor genes, while p53 and MMP-9 are intracellular and extracellular genetic products associated with genomic instability and invasive ability.

This study aims to prove that high miR-21 overexpression, p53 expression, and MMP-9 are risk factors for high grade tumor budding in cervical carcinoma. This nested case-control study was conducted at the Anatomical Pathology Laboratory of Balimed Hospital Denpasar and Mangusada Hospital Badung and the Biomolecular Laboratory of Warmadewa University from November 2022 to April 2023.

Paraffin block material was obtained from radical hysterectomy of cervical carcinoma and miR-21 expression was examined using RT qPCR technique, while p53 and MMP-9 expression was examined using immunohistochemistry technique. A total of 40 simple random sampling samples were divided into two groups, each group was 20 low grade tumor budding samples as control group and 20 high grade tumor budding samples as case group. Data analysis using SPSS-24 included descriptive, chi-square, binary logistic regression. Data were presented in the form of tables and narratives.

The results in this study showed that miR-21 overexpression, high expression of mutant p53 and MMP-9 were significantly risk factors for high grade tumor budding in cervical carcinoma (p < 0.05). The risk of high grade tumor budding in miR-21 overexpression was 13.222 times, in high mutant p53 expression was 44.333 times and high MMP-9 expression was 10.524 times. Simultaneously, not all variables were associated with high grade tumor budding, it was found that mutant p53 expression (OR=53.676) had the greatest risk factor strength compared to MMP-9 expression (OR=13.355). This study proves the role of pro-oncogenic and pro-invasive molecular factors in the formation of high grade tumor budding so that it can affect the aggressiveness of cervical carcinoma. 

This examination was chaired by the Dean of FK Unud Prof. Dr. dr. Komang Januartha Putra Pinatih, M.Kes., with a team of examiners:

1. Prof. Dr. dr. I Made Bakta, Sp.PD-KHOM (Promoter)

2. Prof. dr. I Gusti Alit Artha, M.Sc., Sp.PA(K)., MIAC (Copromoter I)

3. Dr. dr. Ida Ayu Ika Wahyuniari, S.Ked., M.Kes (Kopromotor II)

4. Prof. drh. I Nyoman Mantik Astawa, Ph.D.

5. Prof. dr. I Made Ady Wirawan, S.Ked, MPH, Ph.D.

6. Prof. Dr. dr. I Gusti Ayu Sri Mahendra Dewi, Sp.PA., Subsp.O.G.P.(K)

7. Dr. dr. I Nyoman Gede Budiana, Sp.OG., Subsp.Onk

8. Dr. dr. Ni Made Linawati, M.Si

9. Dr. dr. Desak Made Wihandani, M.Kes

10. Dr. dr. Ni Putu Sriwidyani, Sp.PA

While academic invitations are :

1. Dr. Ni Wayan Tianing, S.Si., M.Kes

2. Dr. dr. I Nyoman Wande, S.Ked., Sp.PK

3. Dr. dr. Ni Wayan Winarti, S.Ked., Sp.PA., Subsp.U.R.L(K)

4. Dr. dr. I Wayan Juli Sumadi, Sp.PA., Subsp.M.S(K)

5. dr. Made Winarsa Ruma, S.Ked., Ph.D.

In this exam, Dr. dr. Ni Wayan Armerinayanti, M.Biomed., Sp.PA., was declared to have graduated as the 409th Graduate Doctor of Medical Science Doctoral Study Program with cumlaude predicate.

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